During the first two years of this grant we were able to meet a primary objective by demonstrating with deletion mapping that the chromosomal locus for the enzyme Esterase D (EsD) is closely linked to that for deletion retinoblastoma on chromosome 13. During these studies we obtained preliminary family data that the gene for the dominant form of retinoblastoma is linked to the EsD locus. During the extension of this grant we plan to investigate the linkage relationship between dominant retinoblastoma and EsD through extensive family studies and to define the value of EsD as a marker system for the retinoblastoma gene in informative families. Us of the Esterase D marker system could mean a dramatic improvement in genetic counseling for families in which either siblings of an affected child or fetuses are at risk to develop retinoblastoma. A nationwide Esterase D screening program for the detection of subclinical cases of 13q- syndrome established during the initial grant will be continued in an effort to collect and establish additional cell lines from 13 deletion patients for future sequencing studies on the retinoblastoma gene. We will, in addition collect further data on the frequency of 13 deletion as a cause of retinoblastoma. Since initial cytogenetic evaluations of both primary retinoblastomas and those propagated in the "nude mouse" suggest a unifocal rather than multifocal origin of tumors in one eye of a bilateral case, further investigation will be carried out. During this study we will also examine the possibility that tumor specific chromosome changes may play a role in the etiology of a small percentage of unilateral retinoblastomas. Finally, fibroblast and lymphoblastoid cell lines will be developed from patients with small specific deletions of chromosome 13.